title: Field evaluation of a prototype paper-based point-of-care fingerstick transaminase test.
abstract: Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3-97.7%) agreement in placing visual results into clinically-defined "bins" (<3x, 3-5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87-0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading-obtained in a target clinical environment, as performed by local practitioners-indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America ; Department of Laboratory Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Nira R
authors.initials: NR
authors.lastname: Pollock
authors.forename: Sarah
authors.initials: S
authors.lastname: McGray
authors.forename: Donn J
authors.initials: DJ
authors.lastname: Colby
authors.forename: Farzad
authors.initials: F
authors.lastname: Noubary
authors.forename: Huyen
authors.initials: H
authors.lastname: Nguyen
authors.forename: The Anh
authors.initials: TA
authors.lastname: Nguyen
authors.forename: Sariah
authors.initials: S
authors.lastname: Khormaee
authors.forename: Sidhartha
authors.initials: S
authors.lastname: Jain
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hawkins
authors.forename: Shailendra
authors.initials: S
authors.lastname: Kumar
authors.forename: Jason P
authors.initials: JP
authors.lastname: Rolland
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Beattie
authors.forename: Nguyen V
authors.initials: NV
authors.lastname: Chau
authors.forename: Vo M
authors.initials: VM
authors.lastname: Quang
authors.forename: Cori
authors.initials: C
authors.lastname: Barfield
authors.forename: Kathy
authors.initials: K
authors.lastname: Tietje
authors.forename: Matt
authors.initials: M
authors.lastname: Steele
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Weigl
mesh_terms: D000410:Alanine Transaminase / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods*; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis*; D003906:Developing Countries / Q000191:economics; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D008111:Liver Function Tests / Q000379:methods*; D044085:Microfluidics; D015588:Observer Variation; D010209:Paper; D019095:Point-of-Care Systems; D014744:Vietnam
chemical_list: D000410:Alanine Transaminase